Project Summary/Abstract: Non-fatal opioid overdose is the strongest predictor of a subsequent fatal overdose. Thus, a non-fatal overdose offers a pivotal opportunity to engage the survivor in harm reduction and/or treatment services to reduce the likelihood of a future fatal overdose. ?Knock and Talk? programs are emerging secondary prevention interventions designed to reduce the risk of a future overdose in survivors. Although they differ widely, these programs share three common characteristics: 1) a collaboration between first responders (fire, police and/or emergency medical services) and public health programs (harm reduction, addiction treatment and/or mental health providers); 2) community-based outreach following a nonfatal overdose; and 3) linking of survivors to treatment and overdose prevention services. Since 2015, Knock and Talk (KT) programs have proliferated to more than 60 Massachusetts municipalities. KT programs can promote better outcomes by minimizing the stigma experienced by people who use opioids, reducing overdose risk behaviors, increasing the likelihood of a naloxone rescue, and motivating survivors to enter care. The emergence of KT programs in some Massachusetts municipalities, but not others, affords an unprecedented opportunity to conduct a natural experiment to evaluate the effectiveness of these interventions. Further, the opportunity exists to identify best practices, unintended consequences, implementation barriers and facilitators, and to develop evidence-informed guideline recommendations for these programs. Thus, the specific aims of this proposal are: 1) To complete a comprehensive inventory, including key characteristics, of Massachusetts KT programs using a statewide survey of local public safety and public health agencies; 2) To identify best practices, unintended consequences, and implementation barriers and facilitators using direct observation of KT encounters and qualitative interviews with front line staff and recipients of KT services in a subsample of 20 representative KT programs; 3) To determine the effectiveness of KT programs in reducing opioid overdoses by comparing a) municipalities with and without KT programs and b) municipalities with and without selected key characteristics among KT programs, using interrupted time- series analyses; and 4) To develop KT program guideline recommendations useful to public health and public safety agencies, based on findings from Aims 1-3 and a review of the literature, using a modified Delphi process with a distinguished panel of public health and public safety experts. To accomplish the proposed mixed methods research, we have assembled a highly qualified and accomplished multidisciplinary team with expertise in developing and implementing these partnerships, quasi- experimental causal inference approaches, quantitative survey and formative qualitative methods, and public health law, policy and ethics. We will develop practical and evidence-informed guideline recommendations for public health and public safety agencies implementing and sustaining KT programs.